Combination of laser and human adipose-derived stem cells in repair of rabbit anal sphincter injury: a new therapeutic approach.

BACKGROUND: Anal sphincter injury leads to fecal incontinence. Based on the regenerative capability of laser and human adipose-derived stem cells (hADSCs), this study was designed to assess the effects of co-application of these therapies on anal sphincter recovery after injury. DESIGN: Male rabbits were assigned to equal groups (n = 7) including control, sphincterotomy, sphincterotomy treated with laser (660 nm, 90 s, immediately after sphincterotomy, daily, 14 days), hADSCs (2 × 106 hADSCs injected into injured area of the sphincter immediately after sphincterotomy), and laser + hADSCs. Ninety days after sphincterotomy, manometry and electromyography were performed, sphincter collagen content was evaluated, and Ki67, myosin heavy chain (MHC), skeletal muscle alpha-actin (ACTA1), vascular endothelial growth factor A (VEGFA), and vimentin mRNA gene expression were assessed. RESULTS: The laser + hADSCs group had a higher resting pressure compared with the sphincterotomy (p < 0.0001), laser (p < 0.0001), and hADSCs (p = 0.04) groups. Maximum squeeze pressure was improved in all treated animals compared with the sphincterotomized animals (p < 0.0001), without a significant difference between treatments (p > 0.05). In the laser + hADSCs group, motor unit numbers were higher than those in the laser group (p < 0.0001) but did not differ from the hADSCs group (p = 0.075). Sphincterotomy increased collagen content, but the muscle content (p = 0.36) and collagen content (p = 0.37) were not significantly different between the laser + hADSCs and control groups. Laser + hADSCs increased ACTA1 (p = 0.001) and MHC (p < 0.0001) gene expression compared with laser or hADSCs alone and was associated with increased VEGFA (p = 0.009) and Ki67 mRNA expression (p = 0.01) and decreased vimentin mRNA expression (p < 0.0001) compared with laser. CONCLUSION: The combination of laser and hADSCs appears more effective than either treatment alone for promoting myogenesis, angiogenesis, and functional recovery after anal sphincterotomy.

Prognostic Value of FBXO39 and ETS-1 but not BMI-1 in Iranian Colorectal Cancer Patients

Background: Colorectal cancer (CRC) is one of the most prevalent cancers worldwide. Despite recent progress in diagnosis and treatment, it remains a major health problem and further studies are needed. We here investigated expression profiles of the FBXO39, ETS-1 and BMI-1 genes in CRCs to validate any possible diagnostic/prognostic significance. Material and Methods: Thirty six patients with locally advanced CRC admitted to Hazrate-Rasoul Hospital-Tehran were enrolled. Initially the expression pattern of FBXO39, ETS-1 and BMI-1 genes were determined using RT-PCR in CRC tumor and adjacent normal tissues then real-time RT-PCR was employed to quantify BMI-1 gene expression. Results: FBXO39 expression was restricted to tumor tissues. Interestingly, expression of this gene was detected in all stage-0 tumor samples. There was a significant relation between FBXO39 gene expression and lymph node involvement. The ETS-1 gene was expressed in 66% of all tumor tissues with p-value=0.03 for increase as compared to the adjacent normal samples. In addition, there was a significant relation between ETS-1 gene expression and tumor size and lymph node involvement. RT-PCR demonstrated BMI-1 gene expression in both tumor and normal tissues and quantification by real-time RT-PCR showed no association between BMI-1 levels and CRC clinicopathological features. Conclusion: Expression of FBXO39 and ETS-1 with lymph node involvement may be considered as an alarm for the occurrence of CRC metastasis, and therfore have prognostic value while BMI-1 appears without importance.

AKAP4, SPAG9 and NY-ESO-1 in Iranian Colorectal Cancer Patients as Probable Diagnostic and Prognostic Biomarkers

Background and objectives: Colorectal cancer (CRC) is the most common gastrointestinal cancer and the second leading cause of cancer death in women in the world. Cancer-Testis Antigens (CTAs) are a group of tumor-associated proteins which typically are expressed in normal reproductive cells of men, but their expression in normal somatic cells is silenced. CTAs, due to their limited expression pattern, are considered as promising targets for cancer diagnosis and immuno-therapy. Methods: Expression of AKAP4, SPAG9 and CTAG1B genes from the CTAs family was studied in both tumor and normal tissues of 62 Iranian CRC patients by RT-PCR with the aim of finding biomarkers for early detection and anticipated progression. Statistical analysis was performed SPSS software V22.0 to assess the significance of any associations. Results: Elevated expression of SPAG9 and AKAP4 genes was observed in approximately 66% and 44% of tumours, respectively, as compared to adjacent non-cancerous tissues. While a significant association was found between AKAP4 gene expression and metastasis (P-value: 0.045), expression of the CTAG1B (NY-ESO-1) gene was not observed in our cases. Conclusion: AKAP4 and SPAG9 genes may find use as diagnostic biomarkers for CRC and AKAP4 may play an important role in progression to metastasis.

A new method for treating fecal incontinence by implanting stem cells derived from human adipose tissue: preliminary findings of a randomized double-blind clinical trial.

BACKGROUND: Anal sphincter defects are a major cause of fecal incontinence causing negative effects on daily life, social interactions, and mental health. Because human adipose-derived stromal/stem cells (hADSCs) are easier and safer to access, secrete high levels of growth factor, and have the potential to differentiate into muscle cells, we investigated the ability of hADSCs to improve anal sphincter incontinence. METHODS: The present randomized double-blind clinical trial was performed on patients with sphincter defects. They were categorized into a cell group (n = 9) and a control group (n = 9). Either 6 × 106 hADSCs per 3 ml suspended in phosphate buffer saline (treatment) or 3 ml phosphate buffer saline (placebo) was injected. Two months after surgery, the Wexner score, endorectal sonography, and electromyography (EMG) results were recorded. RESULTS: Comparing Wexner scores in the cell group and the control group showed no significant difference. In our EMG and endorectal sonography analysis using ImageJ/Fiji 1.46 software, the ratio of the area occupied by the muscle to total area of the lesion showed a 7.91% increase in the cell group compared with the control group. CONCLUSION: The results of the current study show that injection of hADSCs during repair surgery for fecal incontinence may cause replacement of fibrous tissue, which acts as a mechanical support to muscle tissue with contractile function. This is a key point in treatment of fecal incontinence especially in the long term and may be a major step forward. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT2016022826316N2 . Retrospectively registered 7 May 2016.

A Panel of Cancer Testis Antigens and Clinical Risk Factors to Predict Metastasis in Colorectal Cancer.

Colorectal cancer (CRC) is the third common carcinoma with a high rate of mortality worldwide and several studies have investigated some molecular and clinicopathological markers for diagnosis and prognosis of its malignant phenotypes. The aim of this study is to evaluate expression frequency of PAGE4, SCP-1, and SPANXA/D cancer testis antigen (CTA) genes as well as some clinical risk markers to predict liver metastasis of colorectal cancer patients. The expression frequency of PAGE4, SCP-1, and SPANXA/D cancer/testis antigen (CTA) genes was obtained using reverse transcription polymerase chain reaction (RT-PCR) assay in 90 colorectal tumor samples including both negative and positive liver metastasis tumors. Statistical analysis was performed to assess the association of three studied genes and clinical risk factors with CRC liver metastasis. The frequency of PAGE4 and SCP-1 genes expression was significantly higher in the primary tumours with liver metastasis when statistically compared with primary tumors with no liver metastasis (P < 0.05). Among all clinical risk factors studied, the lymph node metastasis and the depth of invasion were statistically correlated with liver metastasis of CRC patients. In addition, using multiple logistic regression, we constructed a model based on PAGE4 and lymph node metastasis to predict liver metastasis of CRC.

Combination of pseudocontinent perineal colostomy and appendicostomy: a new approach in the treatment of low rectal cancer.

BACKGROUND: Abdominal perineal resection (APR) with applied colostomy remains the standard treatment for low rectal cancer; however, to date, a very high morbidity rate has been reported. AIMS: The aims of this study were to assess fecal continence, persistence of disease-related symptoms, and quality of life in patients with low rectal cancer after APR and pseudocontinent perineal colostomy and concomitant appendicostomy. METHODS: We included 17 patients with low rectal cancer who underwent APR at our hospital in this cross-sectional study. Following APR, pseudocontinent perineal colostomy and concomitant appendicostomy were performed. Patients then underwent antegrade colonic enema with tap water. Patients' symptoms, fecal continence, and quality of life were evaluated at regular time intervals. RESULTS: After a median follow-up of 12 months, 15 of 17 patients completed the study period. All patients were able to perform an antegrade enema by themselves. Mean continence score was 7 (out of 20) based on the Wexner Scale scoring system. Mean global health status score was 78, physical function was 93, and emotional function was 88. Minor morbidity was observed in 6 patients (40%). CONCLUSION: Pseudocontinent perineal colostomy with appendicostomy provides an acceptable level of continence and functional and emotional improvement in patients with low rectal cancer undergoing APR. Hence, this combinative method could be considered as an alternative for abdominal colostomy in selected patients.

Anal sphincter injuries during hemorrhoidectomy: a multi center study.

Hemorrhoidectomy is the treatment of choice for patients with third or fourth-degree hemorrhoids. Although the majority of surgeons believe that surgical hemorrhoidectomy is the most effective approach with excellent results in the management of hemorrhoid disease, but hemorrhoidectomy is not a simple procedure. One of the complications of this surgery is an injury to anal sphincters that can lead to incontinency in some patients. In this study, we aimed to reveal the percentage of external and internal anal sphincter injuries in surgical hemorrhoidectomy. We prospectively enrolled 128 patients from April 2006 to February 2007. They underwent hemorrhoidectomy in three general hospitals in Tehran. All patients were in grade III or IV and underwent open hemorrhoidectomy (Milligan-Morgan). After surgery, all resected material was histopathologically examined by two expert pathologists and the results confirmed by other one if there is any discrepancy. From all specimens which sent to the pathology department 15.8% (21 Pts.) had muscle fibers that Smooth muscle fibers were seen in 80.5% (17 Pts.) of them and striated muscle fibers were found in 19.5% (4 Pts.). Although hemorrhoidectomy is a safe and effective method for treatment of hemorrhoid, but the inadvertent removal of smooth and striated muscle during open hemorrhoidectomy had raised concerns about its effects on postoperative anorectal function.

A cross-sectional survey of quality of life in colostomates: a report from Iran.

BACKGROUND: Considering the complications that colostomies may cause, patient self-assessments of their social, emotional, physical, sexual and functional conditions may help their surgeons to evaluate the impact of their interventions or use supplementary methods to maintain patient functional status or decrease its loss to the minimum level. The aim of this study was to evaluate the Quality of Life in Iranian patients with colostomies and to compare the age and gender differences among them. METHOD: This cross-sectional study was conducted from 2009 to 2010 to evaluate the quality of life of 96 patients who had undergone surgery for rectal cancer and had permanent colostomies. The European Organization for Research and Treatment of Cancers Quality of Life Questionnaire (EORTC QLQ)-C30 and the EORTC QLQ-CR38 were used to assess patient Quality of Life. RESULTS: The mean scores for the functional subscales were as follows: Physical Function, 70.9 (±2.2); Role Function, 68.4 (±2.6); Emotional Function, 56.9 (±2.7); Cognitive Function, 68.7 (± 2.6); and Social Function, 64.2 (±3.3). The EORTC questionnaires showed significant differences between males and females. Males had better body image scores. Sexual Function and Sexual Enjoyment were impaired in both males and females, but males had significantly higher scores and better roles in Physical and Sexual Functions. More sexual enjoyment problems in older ages were observed in both males and females. CONCLUSION: Having a colostomy was associated with a high level of emotional and sexual function impairment. The differing challenges between males and females should encourage us to design sex-specific interventions that improve the quality of life in this group of patients.

Malignant fibrous histiocytoma of rectum: Report of a case.

Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma of adults, mostly distributed in the thigh, buttock and groin (46%) and presents rarely in the gastrointestinal tract, classified as gastrointestinal stromal tumors (GIST). MFH is regarded as a diagnosis of exclusion, essentially synonymous with an undifferentiated pleomorphic sarcoma. The recent report presents an 80-year-old man with clinical manifestations of rectal bleeding and final diagnosis of MFH of rectum. It seems that radical resection and adjuvant radiation is important in the management strategy of a patient with such a rare rectal tumor.

MDR1 gene polymorphisms: possible association with its expression and clinicopathology characteristics in colorectal cancer patients.

AIM: Over-expression of some genes, such as MDR1, can increase the level of chemotherapy drug afflux and limit the effectiveness of treatment. We aimed to investigate the effect of MDR1 polymorphisms on its expression level and related characteristics in Iranian colorectal cancer patients. METHODS: Tumor, normal mucosal tissue and blood samples from CRC patients and blood samples from healthy controls (n=60) were obtained for genotyping and measuring the expression level of MDR1. RESULTS: The expression of the MDR1 gene showed a significant increase in cancerous regions compared to adjacent normal tissue. Furthermore, the GG2677 genotype was correlated with highest while the AT 2677 genotype was associated with the lowest levels of expression. In addition only the G2677T/A polymorphism showed association with histological grade of colorectal tumors. CONCLUSION: Our study once more emphasizes effects of MDR1 SNPs which may indirectly impact on response to drugs.